Fecal surrogate markers strongly correlate with endoscopic findings in pediatric onset inflammatory bowel disease: a retrospective study in Japan

Ryoko Yoshimura; Takahiro Kudo; Masanori Toda; Kosuke Kashiwagi; Masumi Nagata; Kaori Aoki; Natsuki Ito; Kazuhide Tokita; Nobuyasu Arai; Reiko Kyodo; Masamichi Sato; Eri Miyata; Keisuke Jimbo; Yoshikazu Ohtsuka; Toshiaki Shimizu; Hiromichi Shoji

doi:10.5217/ir.2025.00103

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Original Article Fecal surrogate markers strongly correlate with endoscopic findings in pediatric onset inflammatory bowel disease: a retrospective study in Japan: Ryoko Yoshimura¹, Takahiro Kudo¹, Masanori Toda¹, Kosuke Kashiwagi¹, Masumi Nagata¹, Kaori Aoki¹, Natsuki Ito¹, Kazuhide Tokita¹, Nobuyasu Arai¹, Reiko Kyodo¹, Masamichi Sato¹, Eri Miyata¹, Keisuke Jimbo¹, Yoshikazu Ohtsuka¹, Toshiaki Shimizu², Hiromichi Shoji²; DOI: https://doi.org/10.5217/ir.2025.00103
Published online: December 12, 2025

¹Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan

²Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan

Correspondence to Takahiro Kudo, Department of Pediatrics, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail: t-kudo@juntendo.ac.jp

• Received: January 5, 2025 • Revised: March 25, 2025 • Accepted: April 2, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract
INTRODUCTION
METHODS
RESULTS
DISCUSSION
NOTES
REFERENCES

Abstract

Background/Aims
Endoscopy serves as the gold standard for assessing disease activity in inflammatory bowel disease (IBD). Noninvasive biomarkers have been under exploration as potential alternatives. This study aims to examine the diagnostic effectiveness of fecal immunochemical tests, along with levels of fecal calprotectin (FC) and fecal lactoferrin (FL), in stool samples from patients with early-onset IBD.
Methods
Children with childhood-onset IBD who visited the Department of Pediatrics and Adolescent Medicine at Juntendo University Hospital between August 2019 and July 2023 were included. FC levels, FL levels, and fecal immunochemical test results were measured using a colloidal gold agglutination assay. Fecal biomarker results and endoscopic findings were reviewed retrospectively.
Results
Sixty-five patients had ulcerative colitis (UC), 20 had Crohn’s disease (CD), and 3 had unclassified IBD. The participants, aged 3–27 years (median, 18.0 years), included 56 males and 32 females. Stool samples (n = 1,105) were analyzed, from 803 with UC, 251 with CD, and 51 with IBD. Endoscopic evaluations were conducted in 45 UC patients and 18 CD patients. A significant correlation was found between the FC and FL. These biomarkers were significantly correlated with the endoscopic activity index in both UC and CD patients.
Conclusions
FC is valuable for diagnosing endoscopic inflammation and predicting recurrence. A significant correlation was observed between FC and FL. In patients with UC and CD, both markers strongly correlated with endoscopic activity. Thus, FC and FL can serve as a reliable alternative to endoscopic evaluation in pediatric patients with childhood-onset IBD.
Keywords: Endoscopy; Fecal calprotectin; Fecal occult blood test; Lactoferrin; Inflammatory bowel diseases

INTRODUCTION

Inflammatory bowel disease (IBD) includes ulcerative colitis (UC), Crohn’s disease (CD), and IBD unclassified (IBDU). It causes chronic intestinal inflammation with periods of relapse and remission. As the cause remains unknown and no cure exists, treatment focuses on controlling inflammation and maintaining remission. The Selecting Therapeutic Targets in Inflammatory Bowel Disease study [1] found that reducing systemic inflammation improves outcomes in IBD management, emphasizing the role of endoscopic evaluation [2]. Endoscopy remains the gold standard for monitoring disease. However, its use in pediatric patients is limited due to its invasiveness, time demands, and limited facility availability. This has increased interest in less-invasive alternatives, with fecal biomarkers showing promise.

Fecal calprotectin (FC) is a calcium- and zinc-binding protein released from neutrophils in response to intestinal inflammation [3]. Similarly, fecal lactoferrin (FL), an iron-binding glycoprotein stored in neutrophil granules, is also released during inflammation and excreted in the stool [4]. Both biomarkers reflect neutrophil activity in the stool, providing a more direct measure of local intestinal inflammation than blood-based biomarkers [5]. Furthermore, FC and FL levels remain stable at room temperature for several days, enabling efficient measurement with small stool samples. While many studies have highlighted the utility of FC in pediatric IBD [3,6-10], the accuracy of these biomarkers has not been thoroughly assessed. This study focused on childhood-onset IBD. We simultaneously measured fecal immunochemical test (FIT) results, FC levels, and FL levels in stool samples using the colloidal gold agglutination method which gives rapid results and compared the correlation between these markers and their effectiveness in evaluating activity.

METHODS

1. Patients

This study included patients admitted to the Department of Pediatrics and Adolescent Medicine at Juntendo University Hospital from August 2019 to July 2023, with a confirmed diagnosis of IBD (onset before age 15 years or younger). IBD diagnosis based on endoscopic and histological findings, following the diagnostic criteria and treatment guidelines for UC and CD established by the Investigation and Research Committee for Intractable Inflammatory Bowel Disease, organized by the Japanese Ministry of Health and Welfare [11,12]. If the diagnosis changed, the final diagnosis was used. Endoscopic examinations within 3 months before or after stool testing were included for patients in remission, and those within 1 month for patients who developed the disease or experienced relapse. Data were retrospectively gathered from medical records. Clinical activity was assessed using the Pediatric Ulcerative Colitis Activity Index (PUCAI) for UC and the Pediatric Crohn’s Disease Activity Index (PCDAI) for CD. Endoscopic activity was evaluated using the Mayo Endoscopic Subscore (MES) and UC Endoscopic Index of Severity (UCEIS) for UC, and the Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD. For UC, clinical remission was defined by a PUCAI of <10, with endoscopic remission indicated by an MES of <2 and a UCEIS of <2. For CD, clinical remission was defined by a PCDAI of <10, and endoscopic remission by a SES-CD of <3.

2. Fecal Sampling

During regular visits, patients collected stool samples in sterile containers provided in advance. These samples were assayed at the hospital for FIT, FC, and FL levels using the colloidal gold agglutination method. A single specimen was analyzed using an automatic clinical chemistry analyzer (Hemo Techt NS-Prime; Alfresa Pharma, Osaka, Japan) [13,14]. The measurement kits used were NESCAUTO Cp Auto for FC, Auto Lf-Plus for FL, and NESCAUTO Hb Auto for FIT, and these 3 markers were measured simultaneously in a single stool sample.

3. Statistical Analyses

Spearman’s rank correlation coefficient was used to assess the correlations between stool biomarkers and clinical and endoscopic activity indices. The association between each stool biomarker and the endoscopic activity index score group was evaluated with the Wilcoxon rank-sum test for 2-group comparisons and the Kruskal-Wallis test for 3-group comparisons. Diagnostic accuracy was determined by calculating the area under the curve (AUC) through receiver operating characteristic (ROC) analysis. Cutoff values were set using Youden’s index. All statistical analyses were performed with EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (R Foundation for Statistical Computing, Vienna, Austria) [15].

4. Ethical Considerations

The study adhered to the Declaration of Helsinki and employed the opt-out method. Informed consent was obtained from the patients’ parents or guardians. Approval was granted by the Institutional Ethics Committee of the Juntendo University Hospital (No. 18-272). Participants had the option to decline participation via the Juntendo University Hospital website.

RESULTS

1. Participant Characteristics

Tables 1 and 2 summarize the patient characteristics. During the study period, 88 patients underwent testing, and 1,105 stool samples were collected. Among the 88 patients, 65 had UC, 20 had CD, and 3 had IBDU. Patients were aged 3 to 27 years, including 56 males and 32 females. The median age at examination was 18 years, with a median age at onset of 11 years and a median disease duration of 7 years. In UC, the most common type was E4 (48 patients, 74%), followed by E1 (4 patients, 6%), E2 (11 patients, 17%), and E3 (2 patients, 3%). In CD, the most frequent type was the small intestine-colon type (16 patients, 80%), followed by the small intestine type (1 patient, 5%), and the colon type (3 patients, 15%). Stool samples (n=1,105) were analyzed, with 803 UC cases, 251 CD, and 51 IBDU cases. The median (interquartile range) FIT results, FC levels, and FL levels were 20 ng/mL (10–148), 266 μg/g (83–865), and 74 ng/mL (20–323), respectively (Table 1). Endoscopic examinations were performed in 68 patients (45 with UC, 18 with CD, and 5 with IBDU), and none developed severe conditions according to the endoscopic activity index (Table 2).

2. Correlation Analysis of Fecal Biomarkers

Fig. 1 shows the distribution of fecal biomarker values. A significant correlation was observed between FC and FL across all groups (Spearman’s rank correlation coefficient: all =0.92, UC=0.93, CD =0.90, and IBD-U =0.62). In contrast, the correlations between FIT and FC or FL were weaker, though still significantly positive.

3. Correlation Analysis of Fecal Biomarkers and Endoscopic Activity Index in UC

Fig. 2 presents distribution maps for the MES and UCEIS scores, as well as stool biomarker measurements. All stool biomarkers exhibited significant positive correlations with the endoscopic activity index. The strongest correlation was observed for FIT, followed by FC and FL.

4. FC, FL, and FIT levels Were Compared According to UC Severity Based on Endoscopic Findings

Patients were classified according to the MES into 2 groups: those with endoscopic activity (MES ≥2) and those in endoscopic remission (MES ≤1). Stool biomarker measurements were compared between these groups (Fig. 3). In the MES ≤ 1 group, median fecal biomarker values were 303 μg/g for FC, 93 ng/mL for FL, and 20 ng/mL for FIT. In the MES ≥ 2 group, median values were 1,124 μg/g for FC, 375 ng/mL for FL, and 536 ng/mL for FIT. The MES ≥2 group showed significantly higher levels of all stool biomarkers compared to the MES ≤ 1 group (P<0.05). Based on UCEIS scores, the patients were further categorized into the endoscopic remission group (UCEIS ≤1), mild disease group (UCEIS of 2–4), and moderate disease group (UCEIS of 5–6), with comparisons made among these groups (Fig. 4). In the UCEIS ≤ 1 group, median FC was 229 μg/g, FL level was 28 ng/mL, and FIT value was 15 ng/mL. In the UCEIS 2–4 group, median FC was 927 μg/g, FL was 212 ng/mL, and FIT was 54 ng/mL. The UCEIS 5–6 group showed median values of 2,988 μg/g for FC, 988 ng/mL for FL, and 8,793 ng/mL for FIT. Significant differences were observed among the 3 groups, with increasing stool biomarker levels correlating with higher UCEIS scores (P<0.05).

5. Prediction of Endoscopic Remission Based on FC and FL Levels in UC

A MES of ≤1 was classified as endoscopic remission (negative), and a MES of ≥2 as endoscopically active (positive), both analyzed using ROC (Fig. 5A). For FC, the AUC was 0.76 with a cutoff of 983 μg/g, resulting in 69% sensitivity and 83% specificity. The AUC for FL was 0.73, with a cutoff value of 368 ng/mL, yielding 60% sensitivity and 83% specificity. Similarly, ROC analysis defined endoscopic remission (negative) as UCEIS ≤1 and endoscopically active (positive) as UCEIS ≥2 (Fig. 5B). For FC, the AUC was 0.75, with a cutoff of 927 μg/g, yielding 57% sensitivity and 100% specificity. The AUC for FL was 0.74, with a cutoff of 204 ng/mL, yielding 60% sensitivity and 87% specificity.

6. Correlation Analysis for Fecal Biomarker and Endoscopic Activity Index in CD

The distribution of SES-CD and stool biomarkers is shown in Fig. 6. The Spearman’s correlation coefficients were 0.76 for FC, 0.83 for FL, and 0.68 for FIT, with all markers showing positive correlations.

7. Comparison of Stool Biomarkers by CD Severity Based on Endoscopic Findings

Fig. 7 compares stool biomarker levels across the SES-CD groups: the endoscopically inactive group (SES-CD ≤2), the mild group (SES-CD ≤ 6), the moderate group (SES-CD ≤ 15), and the severe group (SES-CD ≥16). Significant differences were observed in all stool biomarkers (P<0.05).

8. Prediction of Endoscopic Remission by FC and FL Levels in CD

Endoscopic remission (negative) was defined as SES-CD ≤ 2, and endoscopically active (positive) as SES-CD ≥3. ROC analysis (Fig. 8) showed an AUC of 0.96 for FC with a cutoff value of 630 μg/g, yielding 86% sensitivity and 100% specificity. For FL, the AUC was 0.95, with a cutoff value of 79 ng/mL, also yielding 86% sensitivity and 100% specificity.

9. IBD unclassified

In IBDU, comparing the endoscopic activity index with FC, FL, and FIT levels was difficult due to the limited sample of only 4 patients who underwent endoscopy.

DISCUSSION

Data from 1,105 stool samples were analyzed, including only patients with childhood-onset IBD. This is a large sample size for a pediatric study. In our study, stool biomarkers were measured using the gold colloid method. In Japan, the ELISA (enzyme-linked immunosorbent assay) and FEIA (fluorescent enzyme immunoassay) methods have been widely used to measure fecal biomarkers, but it took about 1 week to obtain results. The gold colloid method used in this study could measure FIT, FC, and FL in about 10 minutes from a small amount of stool specimen, so the test results could be used in clinical practice to make decisions about medical treatment without a time lag.

The present study found a modest correlation between FIT and FC, consistent with previous reports in children, but a significant correlation between FC and FL [16]. FC, FL and FIT positively correlated with endoscopic activity indices in UC and CD, as shown in earlier children [6] and all-age studies [17]. In UC, the correlation was strongest for FIT, followed by FC and FL. This result was similar to previous report on adults [18]. In CD, the strongest correlation was with FL, followed by FC and FIT, differing from UC.

Previous studies in adults have shown no correlation between FIT results and SES-CD in adult patients with small intestine- type CD [19]. However, this study found a significant correlation, as the endoscopic activity evaluation included both small and large intestine types. Each fecal biomarker has distinct characteristics, and factors like stool collection methods and bowel movement frequency can influence results. FIT values are also elevated in patients with hemorrhoidal bleeding and menstruation, even without inflammation. FC levels are influenced by intestinal inflammation unrelated to IBD, nonsteroidal anti-inflammatory drugs and proton pump inhibitor use, dietary factors, obesity, and bowel movement frequency. Notably, FC levels are higher in infancy than in adulthood [20-23]. FL levels may increase in patients with rectal cancer, polyps, and breastfed children [24,25]. Additionally, some studies in children [26] and adults [27-29] have shown that FC and FL levels often rise several months before a relapse. In this study, patients in remission, based on the endoscopic activity index, who had high FC and FL levels did not experience recurrence or require therapy changes during follow-up. These findings emphasize the need to understand each test’s unique properties and use them as complementary diagnostic tools alongside clinical evaluations.

The optimal cutoff values for FC in assessing endoscopic remission of UC were 983 μg/g for MES and 927 μg/g for UCEIS, with AUC values of 0.781 and 0.728, respectively. For FL, the optimal cutoff values were 217 ng/mL and 214 ng/mL for MES and UCEIS, with AUC values of 0.737 and 0.726, respectively. Specificity and sensitivity were 87% versus 77% for MES and 58% versus 67% for UCEIS, indicating strong diagnostic performance. These findings highlight FC and FL as reliable markers for assessing endoscopic activity in UC.

The optimal cutoff value for FL in evaluating endoscopic activity in IBD remains inconsistent, with significant variability across studies in children [26] and adults [30-34]. Further research is needed to determine a definitive FL cutoff value for assessing endoscopic remission in pediatric IBD patients. In conclusion, FC and FL were equally useful in predicting endoscopic remission in UC and CD. No difference in usefulness of FC and FL was found among the severity and classification of each disease.

This study has several limitations. First, the retrospective design may have introduced errors in test values due to a time lag of up to 3 months between stool sample collection and endoscopic examination. Second, only 70 patients’ endoscopic findings were analyzed, highlighting the need for a larger sample size and additional studies for more robust conclusions. Third, although the present study showed a good correlation between SES-CD and FIT, stratified analysis was not possible due to the small number of patients with small and large intestinal types of CD, and no conclusions could be drawn regarding the utility of FIT in small intestinal CD. Lastly, patient selection bias may have occurred due to the study’s single-center design. Future research should involve a large, multicenter, prospective study to confirm the correlation between endoscopic findings and stool biomarkers.

In conclusion, a strong correlation was observed between FL and FC measured using the gold colloid method. In patients with UC and CD, significant correlations between the endoscopic activity index and both FC and FL levels were noted. This method serves as an effective and rapid surrogate marker for disease activity, potentially reducing the need for frequent endoscopic examinations in patients with IBD.

NOTES

Funding Source

The authors received no financial support for the research, authorship, and/or publication of this article.

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Author Contributions

Conceptualization; Data curation; Formal analysis: Yoshimura R, Kudo T. Investigation: Yoshimura R, Kudo T, Toda M, Kashiwagi K, Nagata M, Aoki K, Ito N, Tokita K, Arai N, Kyodo R. Methodology; Project administration: Yoshimura R, Kudo T. Resources: Kudo T. Software: Yoshimura R. Supervision: Sato M, Miyata E, Jimbo K, Ohtsuka Y, Shimizu T, Shoji H. Validation; Visualization: Yoshimura R, Kudo T. Writing - original draft: Yoshimura R, Kudo T. Writing - review & editing: Yoshimura R, Kudo T, Toda M, Kashiwagi K, Nagata M, Aoki K, Ito N, Tokita K, Arai N, Kyodo R, Sato M, Miyata E, Jimbo K, Ohtsuka Y, Shimizu T, Shoji H. Approval of final manuscript: all authors.

Additional Contributions

Ms. Yumiko Sakurai (Juntendo University, Tokyo, Japan) provided assistance in processing and measuring the fecal specimens.

Fig. 1.

Distribution map of stool biomarkers. (A) All patients, (B) patients with ulcerative colitis, (C) patients with Crohn’s disease, and (D) patients with inflammatory bowel disease unclassified. FL, fecal lactoferrin; FC, fecal calprotectin; FIT, fecal immunochemical test.

Fig. 2.

Comparisons of fecal biomarker levels in patients with ulcerative colitis by endoscopic activity score. (A) Mayo Endoscopic Subscore (MES). (B) Ulcerative Colitis Endoscopic Index of Severity (UCEIS). FC, fecal calprotectin; FL, fecal lactoferrin; FIT, fecal immunochemical test.

Fig. 3.

Median fecal biomarker levels across different grades of endoscopic activity according to the Mayo Endoscopic Subscore (MES). FC, fecal calprotectin; FL, fecal lactoferrin; FIT, fecal immunochemical test.

Fig. 4.

Median fecal biomarker endoscopic subscore across different grades of endoscopic activity according to the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). FC, fecal calprotectin; FL, fecal lactoferrin; FIT, fecal immunochemical test.

Fig. 5.

AUC for predicting endoscopic disease activity by FC and FL levels. (A) Mayo Endoscopic Subscore of <2. (B) Ulcerative Colitis Endoscopic Index of Severity of <2. FC, fecal calprotectin; FL, fecal lactoferrin; AUC, area under the curve; CI, confidence interval.

Fig. 6.

Comparisons of fecal biomarker levels by endoscopic activity score according to the Simple Endoscopic Score for Crohn’s Disease (SES-CD) in patients with Crohn’s disease. FIT, fecal immunochemical test; FC, fecal calprotectin; FL, fecal lactoferrin.

Fig. 7.

Median fecal biomarker levels across different grades of endoscopic activity according to the Simple Endoscopic Score for Crohn’s Disease (SES-CD). FC, fecal calprotectin; FL, fecal lactoferrin; FIT, fecal immunochemical test.

Fig. 8.

AUC for predicting endoscopic disease activity (Simple Endoscopic Score for Crohn’s Disease <3) based on FC and FL levels. FC, fecal calprotectin; FL, fecal lactoferrin; AUC, area under the curve; CI, confidence interval.

Table 1.

Patient Characteristics

Characteristic	All (n = 88)	UC (n = 65)	CD (n = 20)	IBDU (n = 3)
Male sex, No. (%)	56 (63.6)	39 (60.0)	16 (80.0)	1 (33.0)
Age (yr), median (range)	18 (3–27)	18 (3–27)	18 (9–27)	12 (8–15)
Age at onset (yr), median (range)	11 (1–15)	12 (1–15)	11 (1–15)	10 (1–10)
Disease duration (yr), mean (range)	7 (0–19)	7 (0–18)	7 (0–19)	4 (1–9)
Classification, No. (%)
UC			-	-
E1		4 (6.2)
E2		11 (16.9)
E3		2 (3.1)
E4		48 (73.8)
CD		-		-
Small intestine type			1 (5.0)
Large intestine type			3 (15.0)
Small and large intestine type			16 (80.0)
No. of fecal tests	1,105	803	251	51
FIT (ng/mL), median (IQR)	20 (10–148)	23 (11–264)	17 (9–48)	13 (8–21)
FC (μg/g), median (IQR)	266 (83–865)	331 (101–900)	150 (64–875)	109 (60–163)
FL (ng/mL), median (IQR)	74 (20–323)	83 (23–392)	46 (14–274)	45 (23–97)

UC, ulcerative colitis; CD, Crohn’s disease; IBDU, unclassified inflammatory bowel disease; FIT, fecal immunochemical test; FC, fecal calprotectin; FL, fecal lactoferrin.

Table 2.

Patient Characteristics

Characteristic	UC	CD	IBDU
No. of endoscopies	45	18	5
Age at onset, median (range)	10 (1–15)	12 (3–14)	2 (2–3)
FIT (ng/mL), median (IQR)	45 (15–392)	36 (13–699)	5 (4.8–5.7)
FC (μg/g), median (IQR)	533 (157–1,127)	686 (137–1,163)	79 (70–92)
FL (ng/mL), median (IQR)	125 (22–454)	217 (34–428)	32 (20–46)
Medication at the time of endoscopy
5-ASA	31	16	1
Corticosteroids	8	1	0
Immunomodulator	20	4	4
AZA	5	2	4
6-MP	15	2	0
Biologicals	8	4	4
Infliximab	2	3	0
Vedolizumab	3	1	0
Adalimumab	1	0	4
Golimumab	1	0	0
Mirikizumab	1	0	0
Other^a	8	17	4
Clinical activity, No. (%)
PUCAI
< 10	30 (66.7)
10–30	9 (20.0)
35–60	4 (8.9)
65–85	2 (4.4)
PCDAI
0–10		14 (77.8)
10–30		4 (22.2)
> 30		0
Endoscopic activity, No. (%)
UC MES
0	9 (20.0)
1	20 (44.4)
2	16 (35.6)
3	0
SES-CD
1–2		4 (22.2)
3–6		5 (27.8)
7–15		6 (33.3)
> 15		3 (16.7)
UCEIS
0–1	15 (33.3)
2–4	27 (60.0)
5–6	3 (6.7)
7–8	0

^a Other: UC (8 herbal medicine), CD (14 ED, 3 colchicine), IBDU (4 ED).

UC, ulcerative colitis; CD, Crohn’s disease; IBDU, unclassified inflammatory bowel disease; FIT, fecal immunochemical test; IQR, interquartile range; FC, fecal calprotectin; FL, fecal lactoferrin; 5-ASA, 5-aminosalicylic acid; AZA, azathioprine; 6-MP, 6-mercaptopurine; PUCAI, Pediatric Ulcerative Colitis Activity Index; PCDAI, Pediatric Crohn’s Disease Activity Index; MES, Mayo Endoscopic Subscore; SES-CD, Simple Endoscopic Score for CD; UCEIS, UC Endoscopic Index of Severity.

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Fecal surrogate markers strongly correlate with endoscopic findings in pediatric onset inflammatory bowel disease: a retrospective study in Japan

DOI: https://doi.org/10.5217/ir.2025.00103

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Fecal surrogate markers strongly correlate with endoscopic findings in pediatric onset inflammatory bowel disease: a retrospective study in Japan

Fig. 1. Distribution map of stool biomarkers. (A) All patients, (B) patients with ulcerative colitis, (C) patients with Crohn’s disease, and (D) patients with inflammatory bowel disease unclassified. FL, fecal lactoferrin; FC, fecal calprotectin; FIT, fecal immunochemical test.

Fig. 2. Comparisons of fecal biomarker levels in patients with ulcerative colitis by endoscopic activity score. (A) Mayo Endoscopic Subscore (MES). (B) Ulcerative Colitis Endoscopic Index of Severity (UCEIS). FC, fecal calprotectin; FL, fecal lactoferrin; FIT, fecal immunochemical test.

Fig. 3. Median fecal biomarker levels across different grades of endoscopic activity according to the Mayo Endoscopic Subscore (MES). FC, fecal calprotectin; FL, fecal lactoferrin; FIT, fecal immunochemical test.

Fig. 4. Median fecal biomarker endoscopic subscore across different grades of endoscopic activity according to the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). FC, fecal calprotectin; FL, fecal lactoferrin; FIT, fecal immunochemical test.

Fig. 5. AUC for predicting endoscopic disease activity by FC and FL levels. (A) Mayo Endoscopic Subscore of <2. (B) Ulcerative Colitis Endoscopic Index of Severity of <2. FC, fecal calprotectin; FL, fecal lactoferrin; AUC, area under the curve; CI, confidence interval.

Fig. 6. Comparisons of fecal biomarker levels by endoscopic activity score according to the Simple Endoscopic Score for Crohn’s Disease (SES-CD) in patients with Crohn’s disease. FIT, fecal immunochemical test; FC, fecal calprotectin; FL, fecal lactoferrin.

Fig. 7. Median fecal biomarker levels across different grades of endoscopic activity according to the Simple Endoscopic Score for Crohn’s Disease (SES-CD). FC, fecal calprotectin; FL, fecal lactoferrin; FIT, fecal immunochemical test.

Fig. 8. AUC for predicting endoscopic disease activity (Simple Endoscopic Score for Crohn’s Disease <3) based on FC and FL levels. FC, fecal calprotectin; FL, fecal lactoferrin; AUC, area under the curve; CI, confidence interval.

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Fecal surrogate markers strongly correlate with endoscopic findings in pediatric onset inflammatory bowel disease: a retrospective study in Japan

Characteristic	All (n = 88)	UC (n = 65)	CD (n = 20)	IBDU (n = 3)
Male sex, No. (%)	56 (63.6)	39 (60.0)	16 (80.0)	1 (33.0)
Age (yr), median (range)	18 (3–27)	18 (3–27)	18 (9–27)	12 (8–15)
Age at onset (yr), median (range)	11 (1–15)	12 (1–15)	11 (1–15)	10 (1–10)
Disease duration (yr), mean (range)	7 (0–19)	7 (0–18)	7 (0–19)	4 (1–9)
Classification, No. (%)
UC			-	-
E1		4 (6.2)
E2		11 (16.9)
E3		2 (3.1)
E4		48 (73.8)
CD		-		-
Small intestine type			1 (5.0)
Large intestine type			3 (15.0)
Small and large intestine type			16 (80.0)
No. of fecal tests	1,105	803	251	51
FIT (ng/mL), median (IQR)	20 (10–148)	23 (11–264)	17 (9–48)	13 (8–21)
FC (μg/g), median (IQR)	266 (83–865)	331 (101–900)	150 (64–875)	109 (60–163)
FL (ng/mL), median (IQR)	74 (20–323)	83 (23–392)	46 (14–274)	45 (23–97)

Characteristic	UC	CD	IBDU
No. of endoscopies	45	18	5
Age at onset, median (range)	10 (1–15)	12 (3–14)	2 (2–3)
FIT (ng/mL), median (IQR)	45 (15–392)	36 (13–699)	5 (4.8–5.7)
FC (μg/g), median (IQR)	533 (157–1,127)	686 (137–1,163)	79 (70–92)
FL (ng/mL), median (IQR)	125 (22–454)	217 (34–428)	32 (20–46)
Medication at the time of endoscopy
5-ASA	31	16	1
Corticosteroids	8	1	0
Immunomodulator	20	4	4
AZA	5	2	4
6-MP	15	2	0
Biologicals	8	4	4
Infliximab	2	3	0
Vedolizumab	3	1	0
Adalimumab	1	0	4
Golimumab	1	0	0
Mirikizumab	1	0	0
Other^a	8	17	4
Clinical activity, No. (%)
PUCAI
< 10	30 (66.7)
10–30	9 (20.0)
35–60	4 (8.9)
65–85	2 (4.4)
PCDAI
0–10		14 (77.8)
10–30		4 (22.2)
> 30		0
Endoscopic activity, No. (%)
UC MES
0	9 (20.0)
1	20 (44.4)
2	16 (35.6)
3	0
SES-CD
1–2		4 (22.2)
3–6		5 (27.8)
7–15		6 (33.3)
> 15		3 (16.7)
UCEIS
0–1	15 (33.3)
2–4	27 (60.0)
5–6	3 (6.7)
7–8	0

Table 1. Patient Characteristics

UC, ulcerative colitis; CD, Crohn’s disease; IBDU, unclassified inflammatory bowel disease; FIT, fecal immunochemical test; FC, fecal calprotectin; FL, fecal lactoferrin.

Table 2. Patient Characteristics

Other: UC (8 herbal medicine), CD (14 ED, 3 colchicine), IBDU (4 ED).